Solution structure of the second bromodomain of Brd2 and its specific interaction with acetylated histone tails

BMC Structural Biology
Hongda HuangYunyu Shi

Abstract

Brd2 is a transcriptional regulator and belongs to BET family, a less characterized novel class of bromodomain-containing proteins. Brd2 contains two tandem bromodomains (BD1 and BD2, 46% sequence identity) in the N-terminus and a conserved motif named ET (extra C-terminal) domain at the C-terminus that is also present in some other bromodomain proteins. The two bromodomains have been shown to bind the acetylated histone H4 and to be responsible for mitotic retention on chromosomes, which is probably a distinctive feature of BET family proteins. Although the crystal structure of Brd2 BD1 is reported, no structure features have been characterized for Brd2 BD2 and its interaction with acetylated histones. Here we report the solution structure of human Brd2 BD2 determined by NMR. Although the overall fold resembles the bromodomains from other proteins, significant differences can be found in loop regions, especially in the ZA loop in which a two amino acids insertion is involved in an uncommon pi-helix, termed piD. The helix piD forms a portion of the acetyl-lysine binding site, which could be a structural characteristic of Brd2 BD2 and other BET bromodomains. Unlike Brd2 BD1, BD2 is monomeric in solution. With NMR perturbation st...Continue Reading

References

May 25, 1992·Nucleic Acids Research·S R HaynesI B Dawid
Jan 1, 1996·Immunogenetics·L Salter-CidM Flajnik
May 1, 1997·Trends in Biochemical Sciences·F JeanmouginR Losson
Sep 23, 1997·Journal of Molecular Biology·M OttigerK Wüthrich
Mar 26, 1998·Protein Science : a Publication of the Protein Society·R Aurora, G D Rose
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·Y W JiangR D Kornberg
Jul 15, 1999·Nature Structural Biology·F Winston, C David Allis
Jan 19, 2000·Nature·B D Strahl, C David Allis
Apr 8, 2000·Current Opinion in Genetics & Development·C L Peterson, J L Workman
Aug 17, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Bryan M Turner
Nov 25, 2000·Journal of Molecular Biology·B P HudsonP E Wright
Aug 7, 2001·Frontiers in Bioscience : a Journal and Virtual Library·P FileticiP Ballario
Aug 7, 2001·Frontiers in Bioscience : a Journal and Virtual Library·B Florence, Douglas V Faller
Aug 11, 2001·Science·T Jenuwein, C David Allis
Sep 5, 2001·Frontiers in Bioscience : a Journal and Virtual Library·A H HassanJ L Workman
Apr 5, 2002·Molecular Cell·Shiraz MujtabaMing-Ming Zhou
Nov 7, 2002·Cell·Bryan M Turner
Nov 7, 2002·Cell·Theodora AgaliotiDimitris Thanos
Oct 18, 2003·Blood·Rebecca J GreenwaldGerald V Denis
Jun 9, 2004·Trends in Cell Biology·Alejandra Loyola, Genevieve Almouzni
Nov 19, 2004·The Biochemical Journal·Anupama SinhaGerald V Denis
Dec 7, 2006·The Journal of Biological Chemistry·Yoshihiro NakamuraShigeyuki Yokoyama

Citations

Sep 22, 2011·Expert Reviews in Molecular Medicine·Susanne MüllerStefan Knapp
Jan 6, 2010·The Journal of Biological Chemistry·Takashi UmeharaShigeyuki Yokoyama
Aug 3, 2014·Archives of Toxicology·Antonella Di CostanzoLucia Altucci
Jun 20, 2012·FEBS Letters·Panagis Filippakopoulos, Stefan Knapp
Mar 21, 2009·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Enyuan ShangDebra J Wolgemuth
Jul 9, 2013·Cancer Treatment Reviews·Pasano Bojang, Kenneth S Ramos
Feb 22, 2013·Journal of Neurodevelopmental Disorders·Junlin LiXiaocai Gao
May 29, 2013·FEBS Letters·Sandra SteinerAmedeo Caflisch
Oct 23, 2016·Drug Discovery Today. Technologies·Kazuki Sasaki, Minoru Yoshida
Jun 14, 2017·Nucleic Acids Research·Stefan J Tekel, Karmella A Haynes
Jul 12, 2017·Journal of Biomolecular Structure & Dynamics·Shruti MathurBalasundaram Padmanabhan
Nov 12, 2010·Nature·Edwige NicodemeAlexander Tarakhovsky
Feb 14, 2020·International Journal of Molecular Sciences·Marian SchererMarion Scheibe
Jun 1, 2016·Journal of Biosciences·Balasundaram PadmanabhanShailesh Tripathi
Aug 2, 2011·Molecular BioSystems·Martin PhilpottTom D Heightman
Feb 7, 2020·Nature Communications·Qifang Xu, Roland L Dunbrack
Nov 29, 2020·Protein Science : a Publication of the Protein Society·Karishma PatelJoel P Mackay
May 19, 2012·Journal of Cell Science·Pablo Garcia-GutierrezMario Garcia-Dominguez

Datasets Mentioned

BETA
M80613

Methods Mentioned

BETA
acetylation
NMR
circular dichroism
chemical shift
gel-filtration
restriction digest
PCR
gel filtration
total correlation spectroscopy

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Spatio-Temporal Regulation of DNA Repair

DNA repair is a complex process regulated by several different classes of enzymes, including ligases, endonucleases, and polymerases. This feed focuses on the spatial and temporal regulation that accompanies DNA damage signaling and repair enzymes and processes.

Glut1 Deficiency

Glut1 deficiency, an autosomal dominant, genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose across the blood brain barrier, is characterized by mental and motor developmental delays and infantile seizures. Follow the latest research on Glut1 deficiency with this feed.

Hereditary Sensory Autonomic Neuropathy

Hereditary Sensory Autonomic Neuropathies are a group of inherited neurodegenerative disorders characterized clinically by loss of sensation and autonomic dysfunction. Here is the latest research on these neuropathies.

Separation Anxiety

Separation anxiety is a type of anxiety disorder that involves excessive distress and anxiety with separation. This may include separation from places or people to which they have a strong emotional connection with. It often affects children more than adults. Here is the latest research on separation anxiety.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.